A Multicenter, Prospective, Randomized Controlled Study Comparing Glucocorticoid Combined With Sirolimus With Monotherapy of Glucocorticoid in the Treatment of Newly Diagnosed Mild Autoimmune Hemolytic Anemia (sirolimus)

This study is a prospective, multicenter, randomized controlled trial. A total of 216 adult patients with newly diagnosed wAIHA were planned to be included and randomly assigned in a 1:1 ratio to the experimental group (glucocorticoid combined with sirolimus) or the control group (glucocorticoid monotherapy). The initial dose of sirolimus in the experimental group was 1mg/d, adjusted according to the blood drug concentration. The target concentration was 4-12ng/mL, and the treatment course was 6 months. Both groups of hormones were gradually reduced according to the standard protocol. All patients were followed up for 24 months, and the differences between the two groups at endpoints such as the hormone-free sustained response rate at the 12th month were compared.

Study Overview

• Status: Not yet recruiting
• Conditions: Autoimmune Hemolytic Anemia (AIHA)
• Intervention / Treatment: Drug: Glucocorticoids

Detailed Description

This study was a randomized controlled study. Two groups of patients were randomly assigned in a 1:1 ratio to receive the following treatment regimens:

1. Glucocorticoid monotherapy group Prednisone at a dose of 1-2 mg/kg/d (or an equivalent dose of methylprednisolone) is taken orally for 2-3 weeks, and then the dosage is reduced regularly. The total course of treatment is approximately 3-6 months. The reduction plan was formulated by the researchers based on clinical practice.
2. Glucocorticoid combined with sirolimus group Glucocorticoids: The usage, dosage and reduction regimen are the same as those in the monotherapy group. | Sirolimus: Starting dose 1 mg/d, orally, once a day. After reaching a steady state 7 to 14 days of medication, monitor the trough concentration. The target trough concentration range is 4 to 12 ng/mL. Adjust the dosage based on the results of blood drug concentration monitoring. The total course of treatment for sirolimus is 6 months. If grade ≥3 related adverse events or trough concentration > occur; 12 ng/mL. Consider reducing the dosage or suspending the administration

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shuangfuyuan, NO I.
    • Beijing, Shuangfuyuan, NO I., China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old, gender not limited;
2. Diagnosed as newly diagnosed wAIHA and requiring systemic immunosuppressive therapy (those with short-term hormone exposure of ≤2 weeks before enrollment can be included)
3. After a comprehensive rheumatology and immunology assessment, there is no evidence of clinical organ involvement in SLE or other connective tissue diseases (only serological abnormalities can be included).
4. Positive Coombs test (IgG type, IgG+C3d type, or only C3d type with a condensed agglutinin titer of 1:64);
5. Active hemolytic anemia, hemoglobin (HGB) ≤ 100 g/L;
6. Liver and kidney function: Alanine aminotransferase (ALT) < 3 times the upper limit of the normal value (ULN), isolated elevation of aspartate aminotransferase (AST) (normal ALT) is acceptable; Serum creatinine ≤2×ULN;
7. Eastern Cooperative Oncology Group (ECOG) Performance status score ≤2 points;

8. Those with a history of malignant tumors must meet the following conditions:

   Radical treatment has been achieved; The disease-free survival period complies with the protocol provisions (such as ≥1 year for basal cell carcinoma, ≥5 years for early solid tumors, ≥5 years for curable lymphoma, etc.); There is currently no evidence of recurrence. Those who do not meet the above conditions (such as CLL, advanced solid tumors, and active tumors) are not included.

9. Voluntarily sign a written informed consent form.

Exclusion Criteria:

1. Pregnant or lactating patients;
2. Clinically confirmed SLE or other definite connective tissue diseases;
3. Secondary AIHA secondary to lymphoproliferative diseases, other hematological malignancies, solid tumors, infections, and drugs;
4. Cold-resistant type or hybrid type AIHA;

5. Received before group enrollment:

   Other immunosuppressants (such as rituximab, cyclosporine, etc., regardless of the duration); Glucocorticoid treatment for more than 2 weeks;

6. Severe cardiac insufficiency (NYHA grade III/IV, or LVEF < 40%);
7. Currently active malignant tumors, or previous tumors that do not meet the requirements of Article 8 of the inclusion criteria;
8. Chronic active infections (active tuberculosis, active hepatitis B/C, etc.);
9. Severe immunodeficiency diseases, HIV infection (CD4⁺ < 200/μL), currently using other potent immunosuppressants, and using targeted biological agents within the last 3 months;
10. Have a history of severe allergy to sirolimus, glucocorticoids or related excipients;
11. Other circumstances where the researcher deems it inappropriate to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glucocorticoid; Glucocorticoid monotherapy group Prednisone at a dose of 1-2 mg/kg/d (or an equivalent dose of methylprednisolone) is taken orally for 2-3 weeks, and then the dosage is reduced regularly. The total course of treatment is approximately 3-6 months. The reduction plan was formulated by the researchers based on clinical practice.	Drug: Glucocorticoids; Glucocorticoids combined with sirolimus
Experimental: Glucocorticoids combined with Sirolimus; Glucocorticoids: The usage, dosage and reduction regimen are the same as those in the monotherapy group. | Sirolimus: Starting dose 1 mg/d, orally, once a day. After reaching a steady state 7 to 14 days of medication, monitor the trough concentration. The target trough concentration range is 4 to 12 ng/mL. Adjust the dosage based on the results of blood drug concentration monitoring. The total course of treatment for sirolimus is 6 months. If grade ≥3 related adverse events or trough concentration > occur; 12 ng/mL. Consider reducing the dosage or suspending the administration.	Drug: Glucocorticoids; Glucocorticoids combined with sirolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The 12-month sustained remission rate	Defined as the proportion of patients who simultaneously met the following conditions at the 12th month after randomization: Discontinue glucocorticoids (or only use prednisone ≤5 mg/d or an equivalent dose for maintenance); Has not received any follow-up treatment for wAIHA;; Still in complete remission (CR) or partial remission (PR) status.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	The incidence of adverse events (AE), serious adverse events (SAE), and grade ≥3 AE;; Adverse events of particular concern: infections (especially opportunistic infections), metabolic disorders (new-onset diabetes, dyslipidemia), bleeding events, hormone-related adverse events (Cushing's syndrome, hypertension, osteoporosis, etc.);; The proportion of patients who discontinued medication, reduced dosage or interrupted treatment due to adverse events	1，3，6，12 months

Collaborators and Investigators

• Sponsor: Chen Miao

Publications and helpful links

General Publications

• 1.Birgens H, Frederiksen H, Hasselbalch HC, et al. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia. Br J Haematol. 2013;163(2):244-252.https://doi.org/10.1111/bjh.12541. 2.Kuter DJ. Warm autoimmune hemolytic anemia and the best treatment strategies. Hematology Am Soc Hematol Educ Program. 2022;2022(1):393-402.https://doi.org/10.1182/hematology.2022000405. 3.Murakhovskaya I, Crivera C, Leon A,et al. Healthcare resource utilization of patients with warm autoimmune hemolytic anemia initiating first line therapy of oral corticosteroids with or without rituximab. Ann Hematol. 2024;103(2):521-533.https://doi.org/10.1007/s00277-023-05613-8. 4.Berentsen S. Treatment of autoimmune hemolytic anemia: novel and investigational approaches. Minerva Med. 2025;116(2):145-158.https://doi.org/10.23736/S0026-4806.25.09617-X. 5.Ciudad M, Ouandji S, Lamarthée B, et al. Regulatory T-cell dysfunctions are associated with increase in tumor necrosis factor α in autoimmune hemolytic anemia and participate in polarization. Haematologica. 2023;108(11):3012-3025. https://doi.org/10.3324/haematol.2023.282859. 6.中华医学会血液学分会红细胞疾病（贫血）学组. 中国成人自身免疫性溶血性贫血诊疗指南（2023年版）[J]. 中华血液学杂志,2023,44(01)：12-18. DOI:10.3760/cma.j.issn.0253-2727.2023.01.003

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: April 4, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: autoimmune hemolytic anemia
• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Hematologic Diseases; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Anemia, Hemolytic, Autoimmune; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pharmacologic Actions; Chemical Actions and Uses; Adrenal Cortex Hormones; Glucocorticoids
• Other Study ID Numbers: GC vs. GC+Sirolimus

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No